AB0001 ALLELIC POLYMORPHISM OF INFLAMMATORY CYTOKINES GENES FOR PREDICTION OF CARDIOVASCULAR DISORDERS IN CHILDREN WITH JIA
Authors: A. Artsymovych, O. Oshlianska
Journal: Annals of the Rheumatic Diseases (2022)

Background It is known that defects in the synthesis and structure of cytokines or their receptors can lead to modification of many pathological processes in the organism: inflammation, coagulation, impaired cell regeneration, which makes it appropriate to further study the genetic preconditions for the violation of immunoregulatory mechanisms. Great attention is paid to the study of allelic polymorphism of genes in chronic inflammatory diseases as a potential marker of functional activity of proteins encoded by them and related features of the course of various disease. Objectives To assess the impact of allelic polymorphism of TNFα (G308A) &amp; IL6 (G174C) genes on the development of cardiovascular disorders in children with JIA. Methods 102 children with JIA were examined. Allelic polymorphism of TNFα (G308A)&amp; IL6 (G174C) genes was determined by PCR using specific oligonucleotide primers, subsequent analysis of polymorphism of restriction fragments was made. Activity of disease was calculated using JADAS27. Functional state of the myocardium was assessed using software-hardware complex “Cardioplus P”, an ECG of 4 th generation. Cluster analysis of obtained data was performed. K-means and EM algorithms were used. The number of children who finally entered this stage of the analysis was 25. Results According to the disease activity, the number of mutations and the complex indicator of the functional state of the myocardium (CI FS, %), two clusters were identified. In cluster 1 (10 children, group 1) the higher score of CI FS (median 78%) and lower disease activity degree (JADAS 27 median 9.5) was noted, and in cluster 2 (15 children, group 2) high disease activity (JADAS 27 median 14) was observed and a decrease in the CI FS (median 62%). The CI FS according to the ECG of 4 th generation differed significantly ( p = 0.00001) in clusters. It is noted that in the second group the disease debuted relatively earlier (p&gt;0.01). Among these cluster groups of patients with JIA there were a number of significant differences in general clinical laboratory parameters: the activity of AST in the blood of patients with JIA was 29±3.1 IU/ l in the first group vs 24±2.2 IU/l in the second group (p = 0.07 Wald-Wolfowitz), serum creatinine was higher in the first group 68.8±11.0 μmol/l (against 57.0±9.3 μmol/l in the second group; t = -2.24, p = 0.044), also in the second group according to the results of the study according to the general analysis of blood there was leukocytosis (11.6±4.1 x10 9 vs. 6.69±0.8 x10 9 , p = 0.075 Wald-Wolfowitz). According to the obtained data of the cluster analysis, the total number of mutations in the genes IL6 and TNF-α was significant for the course of disease. In cases with a larger number of mutations, a more aggressive course of the disease, a more pronounced degree of inflammation, a higher frequency of extra-articular lesions, including changes in the CVS, was noted. Conclusion The overall number of mutations in TNFα (G308A) &amp; IL6 (G174C) genes makes impact on the course of the disease; two and more mutations are associated with a more aggressive course of the disease and can lead to cardiovascular lesions more likely. Determination of allelic polymorphism should be recommended to patients who have changes on ECG performed by a 4th generation ECG. Disclosure of Interests None declared